Our previous studies, from 1961 to date, have demonstrated that glucan, isolated from Saccharomyces cerevisiae, is a unique reticuloendothelial (RE) stimulationg agent which induces a profound enhancement in both humoral and cell-mediated immunity. Since both the induced hyperfunction and hypertrophy of the RES are reversible in nature, glucan is a unique agent to evaluate the role of macrophages in immunophysiology. Relative to the antitumor effect of glucan, the intravenous administration of glucan is associated with inhibition of tumor growth as well as an enhancement in survival of mice and rats when challenged with certain allogeneic and syngeneic tumor models. More recently, experimental studies have demonstrated the ability of glucan to modify infections in mice due to S. aureus, Candida albicans, Sporotrichum shenckii, Cryptococcus neoformans and Mycobacterium leprae. The proposed research provides for 1) the continued development of glucan, water-soluble fractions of glucan and related molecules as potential therapeutic modalities. To this end, preclinical toxicity studies will be undertaken to support, at an appropriate future date, an application to the Food and Drug Administration for an IND in order to pursue an evaluation of the effectiveness of glucan in the therapy of malignant and/or infectious diseases. The influence of low molecular weight water-soluble fractions of glucan on growth of syngeneic melanoma and adenocarcinoma tumors and survival of tumor bearing mice will be studied. Similarly, the comparative ability of these fractions and particulate glucan to enhance host responses to certain bacterial, fungal and viral challenges will be ascertained. From the composite experimental data obtained to date, coupled with biochemical rationale, extensive evidence of tumor reduction and prolonged survival in a variety of allogeneic and syngeneic animal models and preliminary studies of antitumor activity upon intralesional administration in man in the absence of toxicity to doses of 200 to 400 mg, glucan appears to offer unique and significant potential in therapy and prophylaxis in conditions of neoplasia, infection and possible immunodeficient states.